The proposed studies will use innovative approaches to expand the use of iPS to change treatment paradigms for NIDDK-related diseases. We therefore hypothesize that murine iPS cell derived mesenchymal stem cells and adipocytes offer the potential for cell-based therapy to treat lipodystrophy. We propose to create a set of mouse iPS cell models of lipodystrophy using transgene-free approaches for the purpose of evaluating the differentiation potential of young versus aged derived iPS relative to BM-MSC to mesenchymal and adipose lineages and subsequent function. We will also test the ability of the iPS cell derived mesenchymal stem cells to rescue a mouse model of lipodystrophy relative to BM-MSC. This model will enable us to identify a cell type which may be suited as a potential therapy. Additionally, these studies will generate important resources and reagents that will be of vast interest to both the scientific and medical communities.